High flow nasal therapy system

ABSTRACT

A high flow nasal therapy system ( 1 ) has a gas supply ( 2 ), a nebulizer ( 12 ), and a nasal interface ( 7 ). There are two branches ( 11, 10 ) and a valve ( 6 ) linked with the controller, the branches including a first branch ( 11 ) for delivery of aerosol and a second branch ( 10 ) for delivery of non-aerosolized gas. The controller controls delivery into the branches ( 11, 10 ), in which flow is unidirectional in the first and second branches, from the gas supply towards the nasal interface. The first branch ( 11 ) includes the nebulizer ( 12 ) and a line configured to store a bolus of aerosol during flow through the second branch ( 10 ). The valve ( 6 ) comprises a Y-junction between the gas inlet on one side and the branches on the other side.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/301,318, filed Sep. 30, 2016, which is the U.S. national phase entryunder 35 U.S.C. § 371 of International Application No.PCT/EP2015/057866, filed on Apr. 10, 2015, which claims priority toEuropean Patent Application No. 14164468.2, filed on Apr. 11, 2014. Thecontents of each of these are incorporated herein by reference in theirentirety.

INTRODUCTION

The invention relates to delivery of aerosol to the respiratory tractvia the nasopharynx “high flow nasal therapy” (“HFNT”).

Currently, aerosol can be delivered during HFNT using a vibrating meshnebuliser (or other aerosol generator) and a T-piece positioned in theflow path.

US2008/0017198 (Ivri) describes an aerosol delivery apparatus forpressure-assisted breathing systems.

WO2013/163527 (Medstar Health) describes an aerosol system with aninspiratory limb and an expiratory limb.

US2005/0284469 (Tobia et al) describes a system with a nebulizer and agas monitoring device downstream of the nebulizer.

WO2012/079684/US2014/0290646 (NLI GmbH) describes a nasal inhalationdevice with a controller for applying a pattern to activation of anaerosol generator. This relies on exhalation down a separate dedicatedlimb whilst aerosol is being generated in the inspiratory limb.

WO2005/048982 (Nektar) describes a ventilator circuit with aerosoldelivery, in which there is an inhalation line and an exhalation line.

FR2783431 (System Assistance Medical) describes a nebulizer with mainand secondary ducts.

A major problem with HFNT is that often only small quantities of aerosolare delivered to the patient's respiratory tract, due to losses duringpatient exhalation or droplet impaction in the high flows required forHFNT.

Also, where a jet nebulizer is used for HFNT, it requires 6 to 8 l/minto generate aerosol. This requires that an additional flow be added tothe flow being delivered to the patient, and this additional flow mustbe accounted for. This is problematic during the delivery of HFNTtherapy to paediatrics and neonates who can require flows in the range 1to 3 l/min. The flow required to drive the jet nebuliser would exceedthis flow.

Also, both jet and ultrasonic nebulizers have high residual volumes.Moreover, ultrasonic systems can overheat the medication therebypotentially inactivating/denaturing labile formulations.

The invention addresses these problems.

SUMMARY OF THE INVENTION

According to the invention, there is provided high flow nasal therapysystem comprising:

-   -   a gas supply,    -   a humidifier,    -   a nebulizer,    -   a flow line,    -   a nasal interface or a coupler for connection to an external        interface, and    -   a controller configured to control the system in real time to        vary the aerosol delivery to the nasal interface on a temporal        basis,    -   wherein the controller is configured to provide an increased        aerosol delivery during patient inhalation and reduced aerosol        delivery during patient exhalation.

In one embodiment, the system comprises at least two branches and avalve linked with the controller, the branches including a first branchfor delivery of aerosol and a second branch for delivery ofnon-aerosolized gas, and the controller is configured to controldelivery into the branches, in which flow is unidirectional in the firstand second branches, from the gas supply towards the nasal interface.

In one embodiment, the first branch includes the nebulizer. In oneembodiment, the first branch includes a line configured to store a bolusof aerosol during flow through the second branch.

In one embodiment, the valve comprises a Y-junction between the gasinlet on one side and the branches on the other side. In one embodiment,the valve is configured to perform splitting of inlet gas flow betweenthe branches with a desired proportional split set according to thecontroller. In one embodiment, the first branch has a largercross-sectional area than the second branch.

In one embodiment, the controller is configured to reduce inlet gas flowduring at least some of the time that flow is directed through the firstbranch. In one embodiment, one or both of the branches comprises aheater.

In one embodiment, the first and second branches join at their patientends at a common conduit, and said common conduit is in turn linked withsaid nasal interface or coupler.

In one embodiment, the humidifier is included in the second branch.Preferably, the first branch comprises a heater, and the controller isconfigured to control said heater to provide the first branch with anelevated temperature compared to the second branch.

In one embodiment, the cannula comprises prongs each of which is linkedwith a dedicated one of the first and second branches. In oneembodiment, the first branch includes a restrictor for causing morerestricted flow through said first branch than through the secondbranch.

In one embodiment, the controller is configured to control aerosoldelivery at least partly according to a configured control scheme. Inone embodiment, the configured control scheme is set according to dosagerequirements. Preferably, the controller is configured to controlaerosol delivery according to detection of periods of altered activitysuch as sleep.

In one embodiment, the controller is configured to control aerosoldelivery to remove any rainout building up in a breathing circuit bymeans of temporally varying aerosol output. In one embodiment, thecontroller is configured to control aerosol delivery on the basis thatcontrolling pressure or flows may help avoid wastage of medication.

In one embodiment, the controller is configured to control the gas flowgenerator to reduce the gas flow rate to optimal levels for the durationof aerosol therapy only, and to restore gas flow rates again at end ofdose.

In one embodiment, the controller is configured to control gas flowaccording to detection of end of dose.

In one embodiment, the controller is configured to control aerosoldelivery for protection of equipment. In one embodiment, the systemcomprises a sensor for detecting flow conditions and the controller isadapted to vary the aerosol output at least partly in response to sensedflow conditions. In one embodiment, the sensor comprises a flow meter.In one embodiment, the sensor includes a pressure transducer. In oneembodiment, the sensor is downstream of the nebulizer.

In another aspect, the invention provides a method of operating, by acontroller, a high flow nasal therapy system comprising a gas supply forproviding an inlet gas flow, a humidifier, a nebulizer, a flow line, anasal interface or a coupler for connection to an external interface,the method comprising the controller varying aerosol delivery to thenasal interface on a temporal basis.

In one embodiment, the method comprises the step of the controllerproviding an increased aerosol delivery during patient inhalation andreduced aerosol delivery during patient exhalation.

In one embodiment, the method comprises the steps of:

-   -   providing in the system a sensor to sense patient inhalation and        exhalation,    -   providing in the system, as said flow line, at least a first        branch and a second branch,    -   delivering an inlet gas into the branches, in which:        -   the inlet gas flow is divided between the branches to            provide increased aerosol delivery to the nasal interface            during sensed inhalation and reduced aerosol delivery during            sensed exhalation.

In one embodiment, the method comprises the steps of:

-   -   delivering the inlet gas into the branches so that flow is        unidirectional in the first and second branches, from the gas        supply towards the nasal interface, in a manner to provide        positive ventilator support during both patient inhalation and        exhalation,    -   delivering aerosol in the first branch, and    -   delivering non-aerosolized gas in the second branch.

In one embodiment, the method comprises the step of generating theaerosol in the first branch.

In one embodiment, the method comprises the step of storing a bolus ofaerosol in the first branch during flow through the second branch.

In one embodiment, the method comprises the step of reducing inlet gasflow during at least some of the time that flow is directed through thefirst branch.

In one embodiment, the method comprises the step of heating one or bothof the branches.

In one embodiment, the method comprises the step of humidifying gas inthe second branch using a humidifier located in said second branch. Inone embodiment, the method comprises the step of heating gas in thefirst branch to provide the first branch with an elevated temperaturerelative to gas in the second branch. In one embodiment, the methodcomprises the step of restricting gas flow through said first branchrelative to gas flow through the second branch.

In one embodiment, the method comprises the step of the controllercontrolling aerosol delivery at least partly according to a controlscheme with dosage requirements. In one embodiment, the method comprisesthe steps of detecting patient activity and controlling aerosol deliveryaccording to detected periods of altered activity. In one embodiment,the method comprises said detected activity is sleep.

In one embodiment, the method comprises the step of the controllercontrolling a gas flow generator to reduce the inlet gas flow rateduring aerosol therapy only, and restoring the inlet gas flow rate atend of dose.

According to the invention, there is provided a high flow nasal therapysystem comprising a gas supply, a nebulizer, a flow line, a nasalinterface or a coupler for connection to an external interface, and acontroller, wherein the controller is adapted to control the system tovary the aerosol output on a temporal basis.

In one embodiment, the controller is adapted to perform said control inreal time. In one embodiment, the controller is adapted to provide anincreased aerosol delivery during patient inhalation and reduced aerosoldelivery during patient exhalation. Preferably, the system comprises asensor for detecting flow conditions and the controller is adapted tovary the aerosol output at least partly in response to sensed flowconditions.

In one embodiment, the sensor comprises a flow meter. In one embodiment,the sensor includes a pressure transducer. In one embodiment, the sensoris downstream of the nebulizer.

In another embodiment, the controller is adapted to control one or moreoperating parameters of the nebulizer to vary the output.

In one embodiment, the controller is adapted to vary gas flow rate tovary aerosol output.

In one embodiment, the system comprises at least two branches and avalve linked with the controller, the branches including a first branchfor delivery of aerosol and a second branch for delivery ofnon-aerosolized gas, and the controller is adapted to control deliveryform the branches.

In one embodiment, the first branch includes the nebulizer. Preferably,the first branch includes a line adapted to store a bolus of aerosol forrelease under control of the controller. In one embodiment, the valveprovides a Y-junction between the gas inlet on one side and the brancheson the other side.

In one embodiment, the controller is adapted to control aerosol deliveryat least partly according to a configured control scheme. In oneembodiment, the configured control scheme is set according to dosagerequirements.

In one embodiment, the controller is adapted to control aerosol deliveryaccording to detection of periods of non-activity such as sleep.Preferably, the controller is adapted to control aerosol delivery toremove any rainout building up in a breathing circuit.

In one embodiment, the controller is adapted to control aerosol deliveryon the basis of inspiratory pressure or flows may help avoid wastage ofmedication.

In one embodiment, the controller is adapted to control aerosol deliveryto reduce the gas flow rate to optimal levels for the duration ofaerosol therapy only, and to restore gas flow rates again at the end ofdose. In one embodiment, the controller is adapted to control aerosoldelivery according to detection of end of dose. In one embodiment, thecontroller is adapted to control aerosol delivery for protection ofequipment.

DETAILED DESCRIPTION OF THE INVENTION

The invention will be more clearly understood from the followingdescription of some embodiments thereof, given by way of example onlywith reference to the accompanying drawings in which: —

FIG. 1 is a diagram illustrating a HFNT system of the invention;

FIGS. 2(a) and 2(b) are diagrams showing different arrangements of limbsize extending from the valve which controls flow into and between thelimbs,

FIGS. 3(a) and 3(b) illustrate different control schemes with continuousvariation between the limbs,

FIG. 4 is a set of plots showing emitted dose and respirable doseefficiencies recorded across actively controlled gas flow rates,

FIGS. 5(a) and 5(b) are diagrams showing different arrangements forconnection of the limbs to a cannula, in which each limb feeds a singlecannula prong only, and

FIG. 6 is a diagram illustrating an alternative system.

Referring to FIG. 1 a system 1 comprises a gas inlet 2 feeding aregulator 3, in turn feeding a needle valve 4. This feeds a humidifier 5which actively humidifies the gas and feeds the humidified gas to a flowsplitter valve 6. The latter is in this embodiment an electronic 3-wayvalve from which there are two branches (or “limbs”) leading to a nasalinterface (e.g. cannula, mask, pillow) 7. Control is provided by anelectronic controller 16.

The branches are a first branch 10 which is primarily for receivinghumidified air only (that is to say never exposed to aerosolisedmedicament), and a second branch 11 having a nebulizer chamber 12 and aline 13 for delivery of aerosol carried in the humidified gas. There isalso a sensor to detect patient inhalation and exhalation, in this casea flow meter 15 across the limbs at the patient end. The function of theflow meter 15 is to detect when the patient is inhaling, and thereafterprovide a signal for control of the electronic 3-way valve 6.

The feedback signal from the sensor 15 is only used to change the limbthrough which the airflow is delivered. The positive pressure gas flowis unidirectional and it is not intended, or likely, that the patientexhales back down one or both limbs at any time throughout the breathingcycle. Splitting the unidirectional flow path into two limbs allows foraerosol bolus accumulation in the limb 11 whilst the patient isexhaling. The advantage of aerosol bolus delivery derives from theinhalation of high concentration aerosol medicament with minimalmedicament wastage during exhalation as is a problem with some prior artapproaches.

The bolus will build up in the limb 11 due to the lack of flow throughthis limb during periods of the breath cycle not associated withinhalation. The only activity generated in the limb 11 during theseperiods will be by the aerosol generator releasing aerosol droplets intothe limb. This limb 11 is not sealed proximal to the patient and in thecase of extended periods excess build-up of aerosol may exit limb 11 atthe terminal of the line 13. All aerosol droplets released into the limb11 are potentially available to the patient when required. Thecontroller 16 and the valve 6 actively switch limbs as a means ofaerosol protection.

The apparatus 1 achieves an advantageous means of aerosol protectionwhilst maintaining positive pressure ventilator support duringexhalation continuously at all times. In contrast, in the prior approachof having a dedicated inhalation limb and a dedicated exhalation limb totake the exhalation flow in the opposite direction, there may beeither 1) positive pressure support during exhalation by having theinspiratory limb with a gas flow (preventing the accumulation of anaerosol bolus), or 2) it does not provide positive pressure ventilatorysupport during exhalation.

Advantageously, in the invention described herein there is continuousprovision of ventilatory support.

The gas flow rate in the first branch 11 can be relatively reduced bymeans of a flow restrictor. This may for example be a narrower sectionof tubing, an array of holes in a plate, or by means of the degree towhich the flow splitter 6 opens, allowing for a controlled gas flow topass through. A gas flow rate, for the branch 11 which is lower thanthat passing through the second branch 10 allows for maximal entrainmentof suspended aerosol droplets whilst mitigating the risk of aerosollosses through inertial impaction in high flows.

One or both of the limbs 10 and 11 may in some embodiments be heated bymeans of a heater such as a heated wire in the lumen of the limb oralternatively arranged around the circumference of the limb. Heatedtubing is not a requirement but is desirable. The inner diameters of thelimbs 10 and 11 can be equal. However it is envisaged that the limb 11may have a larger inner diameter than that of the limb 10. Thisarrangement would i) increase the internal volume of the limb such thata larger bolus of aerosol can be stored, ii) reducegravitational/sedimentary and inertial aerosol losses within limb 11during the aerosol bolus-building periods where the gas flow isexclusively passing through the limb 10, and iii) to reduce the velocityof the gas passing through the limb 11 thereby reducing the potentialfor inertial aerosol losses.

Of note, for all combinations of gas flow and limb usage, positivepressure ventilatory support is provided to the patient at all times,i.e. during inhalation, positive pressure ventilatory support isprovided via limb 11, during exhalation, positive pressure ventilatorysupport is provided via limb 10.

FIG. 2(a) illustrates the embodiment where the limbs 11 and 10 are ofequal dimensions, whereas FIG. 2(b) illustrates an embodiment in whichwhere the aerosol limb (11(a)) is wider.

Further, the limb 11 may be extended in length when compared with thelimb 10. Also, the line 13 may in some embodiments be expandable, butthis is not essential. In this embodiment the line 13 is thepost-nebuliser side of branch 11 suitable to be filled with aerosol.

The system 1 delivers aerosol therapy during HFNT. It cyclicallyaccumulates a bolus of aerosol in the line 13, of the branch 11.

The cycle in this embodiment is the breathing cycle and the bolus isaccumulated in the line 13 during exhalation. The flow to the patientreverts to non-aerosol laden humidified air in the branch 10 duringexhalation. Switching is achieved by means of the electronicallycontrolled 3-way valve 6. At all times the flows in the branches aretowards the patient in both of the limbs 11 and 10. The patient'sexhaled gas exits the patient via the mouth and to the air, and aroundthe cannula in the nose to the air. Exhaled gas does not flow down thebranches 11 or 10 as they are pressurised.

The positive pressure gas flow is unidirectional and it is not intended,or likely, that the patient exhales back down one or both limbs at anytime throughout the breathing cycle. Splitting the unidirectional flowpath into two limbs is particularly effective at allowing aerosol bolusaccumulation in the limb 11 whilst the patient is exhaling. This helpsto achieve the inhalation of high concentration aerosol medicament withminimal medicament wastage during exhalation as is the problem in theprior art.

The feedback for the valve 6 control may take the form of a pressurechange (positive or negative, measured with a pressure transducer), flowrate change (measured with a flow meter), respiratory gas (e.g. CO₂measured with an appropriate monitor capable of real time digitaloutputs). Feedback may also take the form of manual user inputs such asbutton presses. The controller may have an “aerosol delivery mode” on asoftware GUI or other user interface. On selection of this mode, thevalve 6 may act according to its preprogramed instructions to regulategas flow between the limbs 10 and 11. Under conditions where the aerosoldelivery mode is not selected, the valve 6 can act to split the gas flowthrough one or both of the limbs 10 and 11 concurrently.

Because the controller prevents gas flow in the branch 11 during patientexhalation, it allows for the accumulation of aerosol as a bolus as itis not cleared from the branch. Accumulation of aerosol as a bolusresults in a high concentration of aerosol being available immediatelyon inhalation, and thereby improves efficiency of aerosol delivery tothe patient.

In alternative embodiments the switching may be according to a differentcontrol scheme. For example, where perhaps a drug may only be suitablefor delivery once every half hour, the controller may operate the valve6 so that the flow is from the branch 11 at this frequency. The systemprovides the flexibility of delivering aerosol either breath-by-breathor for pre-defined portions of treatment. The control scheme may befactory-set or it may in alternative embodiments be configurable by theclinician or by the user.

In all cases, the controlled division between the branches avoids needto dynamically control the output of the nebulizer 12, although this mayadditionally be done. The valve 6 is controlled so that the inlet flowis directed in varying proportions between 0% and 100% between thebranches 11 and 10.

In more detail, upon receipt of the feedback signal;

-   -   a) The 3-way valve switches to limb 11 only, resulting in no gas        flow entering the limb 10 (0 litres per minute (LPM)) and all        gas flow entering limb 11 (X LPM).    -   b) The 3-way valve splits the gas flow between limbs 10 and 11.        The split may take the form of (% of gas flow: % of gas flow)        50:50, 90:10, 25:75 as examples.

These control schemes are illustrated in FIGS. 3(a) and 3(b).

Under these gas flow conditions, the aerosol generator may be activatedor not, depending on the user selected options.

The internal geometries of the line 13 may be different from those ofthe line 10 so as to allow for maximal generation and storage of theaerosol bolus. These differences may include any or all of thefollowing, but are not limited to; the use of smooth tubing as opposedto corrugated tubing, larger internal diameter tubing, longer lengthtubing. Additionally, the internal geometries of the line 13 may bedifferent from those of line 10 so as to allow for alteration of theaerosol carrier gas velocity.

The valve 6 may be controlled according to the needle valve/flowregulator 6 such that when the gas flow is being directed down the limb11, or a combination of limbs 10 and 11, the total gas flow is reducedby the gas flow controller 4. This embodiment is designed to reduceaerosol losses within the limb 11 in an effort to increase the emittedfraction of aerosol. The benefits are illustrated in the plots of FIG. 4.

Referring to FIG. 5(a), in another embodiment an aerosolisation limb 111similar to the limb 11 and a gas-only limb 110 similar to the limb 10feed a nasal cannula 107 with two separate prongs 107(a) and 107(b) eachfor a single nare. In operation, it is likely that gas flow would bedelivered down both limbs 110 and 111 such that the back pressuregenerated by such a restriction would not interfere with gas flow beingdelivered to the patient. A potential advantage is that given aerosolshall enter the nasopharynx via one nostril only there will be no mixingof aerosol streams, thereby increasing aerosol rainout in the naso andoropharynx. Another potential advantage is the alternating of pressurebuild-up between nostrils. It is believed by some that mononasal HFNTreduces intercranial pressure.

In another embodiment, as shown in FIG. 5(b) a limb 210 and a limb 211join at a conduit 215 prior to connection with a cannula 207.

It will be appreciated that the system optimises gas flow rates andaerosol delivery efficiency for HFNT. Positive end expiratory pressurescan be controlled by the caregiver. The system can provide feedback tothe user regarding flow rates and pressures to achieve optimum therapy.

Table 1 lists examples of the logic flows used in this system.

TABLE 1 Logic flow INPUT to system OUTPUT from system User inhalationdetected by 3-way valve switches to pressure transducer allow flow topass through aerosol limb 11 only User exhalation detected by 3-wayvalve switches to pressure transducer allow flow to pass through limb 10only

Referring To FIG. 6 an alternative system 20, comprises:

21=Air inlet

22=Humidifier

23=Nebulizer

24=Flow Meter in line to patient interface

25=Nebulizer power supply and output controller

26=Communication lines between 25 and 21 or 23

27=Patient interface, e.g. nasal cannula

The gas inlet 21 has a regulator feeding a needle valve Z. This feedsthe humidifier 22 which actively humidifies the gas and feeds thehumidified gas to the patient circuit. The patient circuit leads to thenasal interface 27 (for example cannula, mask, and/or pillow). Thesystem control unit 25 houses a standalone flow generator, including butnot limited to a fan.

The gas flow rate within the system can be detected by means of the flowmeter 24 or alternatively by an electronic or mechanical signal suppliedby the regulator, in the case of an integrated device providing bothuser interface and flow generation and regulation. These components areconnected directly with and supply a signal to the nebuliser controller25.

The nebuliser controller 25 controls nebuliser output described asaerosol flow rate (millilitres of medicament aerosolised per minute),aerosol density (number of aerosol droplets per unit volume of gas) orintermittent on-off pulses, of varying durations, of aerosol generation.

The nebuliser 23 may be placed on the gas inlet side of the humidifier22 or the patient side of the humidifier 22, and its operation isdirectly controlled by the nebuliser controller 25. Placement of thenebuliser 23 on the gas inlet side of the humidifier 22 allows forpre-conditioning of the gas prior to humidification. The nebuliser shallideally emit a droplet size in the range of 0.1 to 10 microns MMAD,however droplets up to 20 microns MMAD may find utility in targeting thenasal passages specifically.

Communication between the gas flow generator control unit and/or theflow meter 24 will identify no gas flow conditions that will beconverted to a signal sent to the nebuliser controller 25 and/or thehumidifier 22. In this instance of no-flow, or backward flow (flowcoming from the patient side towards the flow generator) the nebuliser23 and/or the humidifier 22 shall be prevented from generating aerosoland/or humidity. The function of this feature is to protect internalelectronics, fans and other components of the flow generator and controlunit from exposure to aerosol or humidity.

The detection of gas flow rate may result in one of several conditionsincluding, but not limited to; control of the nebuliser output orcontrol of the gas flow rate on a temporary basis.

In the instance where the nebuliser output is controlled, predefinedoutput settings shall be supplied by the controller 25 to the nebuliser23. These output settings may include, but are not limited to: reductionof aerosol output concurrent with high gas flow rates, or alternativelyan increase in nebuliser output concurrent with low gas flow rates. Thefunction of this control is to optimise aerosol delivery to the patient.

In the instance where gas flow rate is controlled, gas flow rates may bereduced or increased on a temporary basis in order to allow foroptimised aerosol delivery to the patient.

In the system 20 gas flow rate can be monitored in the following ways:

-   -   Integrated control of/from electromechanical gas flow generator,        for example standalone fan capable of generating therapeutically        relevant gas flow rates in the range of 0 to 100 litres per        minute.    -   Pressure transducer, which is in fluid communication with gas        flow limb, incorporated into nebuliser controller system.    -   Digital Flow meter, which is in fluid communication with gas        flow limb, incorporated into nebuliser controller system.

Referring again to FIG. 4 , this shows plots for emitted dose andrespirable dose delivery rates across gas flow rates for both high andreduced nebuliser outputs following dynamic nebuliser aerosol outputmonitoring and control. It will be seen that the slopes are similar,both being downward indicating lower dose with increased gas flow.

The data for the plots of FIG. 4 is given in Table 2 below.

TABLE 2 Emitted dose and tracheal dose (expressed as a percentage of thenominal dose placed in the nebuliser prior to test) across 3 standardgas flow rates for both high and reduced aerosol output. Emitted dose(%)¹ Tracheal Dose (%)² Gas Flow Rate High Reduced High Reduced (LitresAerosol Aerosol Aerosol Aerosol per minute) Output Output Output Output15 58.05 ± 62.73 ± 18.95 ± 15.75 ± 1.95 3.05 1.32 0.47  30 47.17 ± 45.96± 12.44 ± 8.50 ± 4.45 2.68 3.72 1.79 45 32.59 ± 37.86 ±  5.81 ± 4.87 ±2.89 4.19 1.40 1.66 NOTES: ¹Emitted dose describes the percentage of thenominal nebuliser dose exiting the system with no simulated patientbreathing. ²Tracheal dose describes the percentage of the nominalnebuliser dose delivered beyond the trachea in a model of a simulatedbreathing adult patient.

Table 3 below lists examples of the logic flows used in this system.

TABLE 3 INPUT to system OUTPUT from system Control unit programmed byNebuliser output altered user to a set flow rate Control unit programmedby Pre-programed software does user to a set flow rate not allowselected gas flow rate to be generated during aerosol therapy Userinformed of suboptimal aerosol delivery conditions Control unitprogrammed by Nebuliser aerosol output user to a set nebuliser aerosolincreased. output Nebuliser aerosol output decreased for optimal aerosoldelivery conditions in high gas flow Nebuliser aerosol output decreasedfor extended e.g. all day or overnight delivery of medication Flowmeterdetects no gas No aerosol generated flow

Aerosol output can be controlled by real-time software monitoring of gasflow rates, and subsequent control of nebuliser power or cycling.

Real-time monitoring of gas flow and concurrent adjustment of aerosoloutput to pre-set levels has applications across several patientinterfaces.

-   -   One primary use may be the day-long, long-term use of high flow        nasal therapy (HFNT). Patients receiving HFNT often wear the        device 24-hours a day and during periods of non-activity (e.g.        sleep) may increase or decrease the gas flow rate to comfortable        levels. During this period, the patient may need to wake up in        order to add more medication to the medication cup, or        alternatively remove any rainout building up in their breathing        circuit.    -   Other examples of single limb, positive pressure-only systems        include non-invasive ventilation systems, e.g. CPAP and BiPAP.        Control of nebuliser output on the basis of inspiratory pressure        or flows may help avoid wastage of medication.    -   In instances where the nebuliser system is integrated into a        standalone gas flow generator or regulator for short term use,        and where therapeutically acceptable, the control mechanism may        be used to reduce the gas flow rate to optimal levels for the        duration of aerosol therapy only, and restoring gas flow rates        again at the end of dose.    -   Protection of equipment. On occasions where the nebuliser        control system is integrated into a standalone gas flow        generator or regulator, the optimal placement of the nebuliser        for respirable dose optimisation may result in aerosol being        generated close to electronics or components that could be        adversely affected by aerosol, e.g. float valves on humidifier        chambers. Detection of a “no-flow” or “low-flow” condition could        be used to prevent generation of aerosol, and thereby protect        the incumbent equipment.

The invention is not limited to the embodiments described but may bevaried in construction and detail. For example the humidifier may belocated in the non-aerosolisation branch only. Where the humidifier isin a common inlet, then it may be controlled to have a reduced or zerooutput when the flow is only through the aerosolized branch. Humidity isknown to alter (increase) droplet size and so under the conditionsdescribed where airflow is directed through the limb 11 the risks ofincreased aerosol losses in humidified air are mitigated.

Also, it is envisaged that the system may include a means of control ofaerosol output to a level deemed appropriate for the gas flow rate beingdelivered (not on the basis of patient-side sensor feedback. In thisembodiment, control of aerosol output is in fluid or digitalcommunication with the gas flow generator. At various gas flow ratesaerosol output can be varied in order to maximise the emitted aerosoldose from the system. Variations in aerosol output can take the form ofon/off, or reduced/increased output. Further, on selection of an“aerosol delivery mode” the system may act to temporarily reduce the gasflow rate for the duration of active aerosol generation. FIG. 4illustrates the effect of varying both aerosol output and gas flow rateon emitted dose from the system. Under conditions where reduced gas flowrates are not appropriate (clinically) aerosol generator output can bevaried to the same effect.

The invention claimed is:
 1. A high flow nasal therapy systemcomprising: a gas supply, a humidifier, a nebulizer, a flow line havinga first branch for delivery of aerosol and a second branch for deliveryof non-aerosolized gas, a nasal interface, and a controller configuredto control the system in real time to vary the aerosol delivery to thenasal interface on a temporal basis, wherein the controller isconfigured to control delivery of inlet gas into the first branch andthe second branch with a desired proportional split between the firstbranch and the second branch to provide aerosolized gas delivery duringpatient inhalation and delivery of non-aerosolized gas during patientexhalation.
 2. The of high flow nasal therapy system claim 1, in whichexhalant does not flow through the first branch or the second branchduring exhalation.
 3. The high flow nasal therapy system of claim 1, inwhich the humidifier is upstream of a split between the first branch andthe second branch with respect to the gas supply.
 4. A high flow nasaltherapy system as claimed in claim 1, further comprising a valve linkedwith the controller, and the controller is configured to controldelivery into the branches, in which flow is unidirectional in the firstand second branches, from the gas supply towards the nasal interface. 5.A high flow nasal therapy system as claimed in claim 4, wherein thefirst branch includes the nebulizer.
 6. A high flow nasal therapy systemas claimed in claim 4, wherein the valve comprises a Y-junction betweena gas inlet on one side and the branches on another side.
 7. A high flownasal therapy system as claimed in claim 4, wherein the valve isconfigured to perform splitting of the inlet gas flow between thebranches with a desired proportional split set according to thecontroller.
 8. A high flow nasal therapy system as claimed in claim 4,wherein the first branch has a smaller cross-sectional area than thesecond branch.
 9. A high flow nasal therapy system as claimed in claim4, wherein the controller is configured to reduce the inlet gas flowduring at least some of the time that flow is directed through the firstbranch.
 10. A high flow nasal therapy system as claimed in claim 4,wherein the first and second branches join at their patient ends at acommon conduit, and said common conduit is in turn linked with saidnasal interface.
 11. A high flow nasal therapy system as claimed inclaim 4, wherein the humidifier is included in the second branch.
 12. Ahigh flow nasal therapy system as claimed in claim 11, wherein the firstbranch comprises a heater, and the controller is configured to controlsaid heater to provide the first branch with an elevated temperaturecompared to the second branch.
 13. A high flow nasal therapy system asclaimed in claim 11, wherein the first branch includes a restrictor forcausing more restricted flow through said first branch than through thesecond branch.
 14. A method of operating, by a controller, a high flownasal therapy system comprising a gas supply for providing an inlet gasflow, a humidifier, a nebulizer, a flow line having a first branch fordelivery of aerosol and a second branch for delivery of non-aerosolizedgas, and a nasal interface, the method comprising: varying, by thecontroller, aerosol delivery to the nasal interface on a temporal basis;controlling, by the controller, delivery of the inlet gas into the firstbranch and the second branch with a desired proportional split betweenthe first branch and the second branch to provide an increased aerosoldelivery during patient inhalation and delivery of non-aerosolized gasduring patient exhalation.
 15. A method as claimed in claim 14, whereinthe high flow nasal therapy system further comprises a sensor fordetecting flow conditions, and wherein the controlling, by thecontroller, the delivery of the inlet gas into the first branch and thesecond branch with a desired proportional split between the first branchand the second branch includes: controlling, by the controller, thedelivery of the inlet gas into the first branch and the second branchwith a desired proportional split between the first branch and thesecond branch to provide increased aerosol delivery to the nasalinterface during sensed inhalation and reduced aerosol delivery duringsensed exhalation.
 16. A method as claimed in claim 15, furthercomprising: delivering, by the controller, the inlet gas into thebranches so that flow is unidirectional in the first and secondbranches, from the gas supply towards the nasal interface, in a mannerto provide positive ventilator support during both patient inhalationand exhalation, delivering, by the controller, aerosol in the firstbranch, and delivering, by the controller, non-aerosolized gas in thesecond branch.
 17. A method as claimed in claim 15, further comprisinggenerating, by the controller, the aerosol in the first branch.
 18. Amethod as claimed in claim 15, further comprising storing a bolus ofaerosol in the first branch during flow through the second branch.
 19. Amethod as claimed in claim 15, further comprising reducing inlet gasflow during at least some of an amount of time that flow is directedthrough the first branch.
 20. A high flow nasal therapy systemcomprising: a gas supply, a humidifier, a nebulizer, a flow line havinga first branch for delivery of aerosolized gas and a second branch fordelivery of non-aerosolized gas, a sensor for detecting flow conditions,a nasal interface or a coupler for connection to an external interface,and a controller configured to: control the system in real time to varythe aerosol delivery to the nasal interface on a temporal basis, anddeliver an inlet gas flow from the gas supply into the first branch andthe second branch, the inlet gas flow being divided between the firstbranch and the second branch to provide aerosolized gas delivery duringsensed inhalation and non-aerosolized gas delivery during sensedexhalation, and wherein the humidifier is upstream of a split betweenthe first branch and the second branch with respect to the gas supply.